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Role of serum amyloid P in skin graft survival and wound healing in burned patients receiving skin grafts
Clinica Chimica Acta 412 (2011) 227–229
Contents lists available at ScienceDirect
Clinica Chimica Acta j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / c l i n c h i m
Role of serum amyloid P in skin graft survival and wound healing in burned patients receiving skin grafts Yi-ming Zhang a,1, Ya-dong Fang b,1, Yi-cheng Wang c, Shao-liang Wang a, Ze-yuan Lei a, Xiao-wei Liu a, Tong-chun Mao a, Dong-li Fan a,⁎ a
Department of Plastic and Cosmetic Surgery, Xinqiao Hospital, Third Military Medical University, Xinqiao Road, Sha Ping Ba District, Chongqing 400037, People's Republic of China State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Burn Research, Third Military Medical University, Southwest Hospital, Gaotanyan Street, Sha Ping Ba District, Chongqing 400038, People's Republic of China c Department of Plastic and Burn Surgery, Hospital of Chongqing Armed Police, Weiguo Road, Nan An District, Chongqing 400061, People's Republic of China b
a r t i c l e
i n f o
Article history: Received 2 June 2010 Received in revised form 12 August 2010 Accepted 10 September 2010 Available online 12 October 2010 Keywords: Serum amyloid P Skin graft Wound healing
a b s t r a c t Background: Recent studies in animal models suggest that serum amyloid P (SAP) can affect burn wound healing. However, the role of SAP in a clinical setting remains unknown. Methods: We enrolled 88 patients with third degree burn wounds. All the patients were candidates for autoskin graft procedure using stamp skin graft. The complete graft healing time and the number of survived grafts were recorded. Serum SAP levels were assessed 1 day before operation. Results: There was no significant difference in SAP level between controls and patients. There were no significant differences noted among the patients with different burn surface area. However, when the patients in each group were stratified by SAP levels, the mean complete healing time of grafted wound and the mean numbers of survived skin grafts were significantly different. Spearman's analyses showed that the serum SAP levels negatively correlated with the complete wound healing time and mean numbers of survived skin grafts. Logistic regression analysis showed that the serum SAP levels and mean numbers of survived skin grafts were potent independent factors contributing to wound healing. Conclusions: The results of this study suggest that the serum SAP levels may be an easy detected predictor for the healing of burn wounds. Crown Copyright © 2010 Published by Elsevier B.V. All rights reserved.
1. Introduction Skin grafting is a simple and common procedure widely used in burned patients to achieve wound closure. The effect of this procedure is mainly dependent on the survival of the grafted skin. A recent study showed that the serum marker, prealbumin, is a sensitive predictor for the graft healing in burned patients [1]. As burn wound healing involves the proliferation and differentiation of fibroblasts and the deposition of extracellular matrix, whether factors associated with fibrotic proliferation and differentiation determine the wound healing process attracts our interest. Serum amyloid P (SAP) is a plasma glycoprotein which was first identified as a protein component of systemic amyloid deposits. SAP is also a potent regulator of organic fibrosis by inhibiting the differentiation of monocytes into fibrocytes [2–4]. Relatively small changes in the circulating levels of SAP may have an important effect on the fibrotic process in vivo. An animal study showed that SAP Abbreviations: SAP, Serum amyloid P; BSA, Burn surface area. ⁎ Corresponding author. Tel.: + 86 023 68755302; fax: +86 023 68755306. E-mail addresses: [email protected], [email protected] (D. Fan). 1 The authors contributed equally to this paper.
delays normal murine dermal wound healing due to increased inhibition of fibrocyte differentiation depleting SAP at a wound site can speed the wound healing and reducing serum amyloid P by a binding hydrogel speeds healing of partial thickness wounds in pigs. All these observations in animal models strongly suggest that SAP [5,6] is an active factor associated with wound healing. To date, there is no clinical study regarding the role of SAP in wound healing in burned patients. In the present study, we explored the association between the serum level of SAP and the wound healing of in burned patients subject to auto-skin graft. 2. Methods 2.1. Patients From Feb 2008 to Aug 2009, we enrolled 88 patients with third degree burn wounds, among which 49 were female and 39 were male with the average age at 43.8 ± 8.1 year. The area of third degree burn wound varied from 5% to 75%. The burn wounds were located in the body trunk and four extremities. According to the burn surface area (BSA), all patients were divided into three groups, namely, G1 (BSA 5– 25%, n = 26), G2 (BSA 25–50%, n = 42) and G3 (BSA 50%–75%, n = 20).
0009-8981/$ – see front matter. Crown Copyright © 2010 Published by Elsevier B.V. All rights reserved. doi:10.1016/j.cca.2010.09.036
228
Y. Zhang et al. / Clinica Chimica Acta 412 (2011) 227–229
All the patients were candidates for auto-skin graft procedure using stamp skin graft. All the patients were on regular oral feeding (no special diet or supplements). The skin grafts were observed daily after operation by 2 burn surgeons to evaluate the wounds healing. Complete graft healing was considered when graft take was more than 90% of graft size and the complete healing time (days) were recorded. The stamp skin grafts tightly attached to the host burn wound bed were considered survival and their number/100 cm2 were recorded. The observation was performed in 3 independent grafted wounds in each patient and the average survival number was calculated. Patients with head and neck burns, and those with connective tissue disease, autoimmune diseases and diabetic mellitus were excluded from the study. Sixty-eight sex and age matched healthy controls were enrolled in this study. 2.2. Serum SAP detection Serum SAP levels were assessed 1 day before operation by ELISA method as follows: microtitre plates were coated in 0.01 mol/l PBS with 2 mg/ml of a monoclonal antibody directed against SAP (1:1500, Santa Cruz Biotechnology, Santa Cruz, CA) for 1 h. After washing, sera were added starting at a 250-fold dilution, with a further fourfold dilution in 0.05 mol/l Tris, 0.3 mol/l NaCl, 1% BSA, and 0.05% Tween-20 for 1 h. A reference serum was added as a positive control. Monoclonal antibody conjugated with horseradish peroxidase directed against human SAP (1:2000, Santa Cruz Biotechnology) was applied for 30 min using an ELISA shaker in the dark. 2.3. Statistical analysis Data were expressed as mean value and SD. Statistical significance of the correlation was determined by Spearman's coefficient. Student's t test and χ2 test were used to evaluate significance in clinical characteristics between the two groups. A p b 0.05 was considered significant. 3. Results Table 1 summarized the clinical characteristics in cases and controls. There are no significant differences in age, sex, prevalence and the percentage of smokers between cases and controls (all P = NS). The mean SAP level in controls was 24.5 ± 4.5 mg/l, while in patients was 25.4 ± 2.8 mg/l, no significant differences were observed (P = NS). Fig. 1 shows the SAP level distribution in the burned patients according to their BSA. There were no significant differences noted among the G1, G2 and G3 groups. The overall mean SAP level in all patients was 25.4± 2.8 mg/l. According to the overall mean SAP level, all the patients in each group were stratified into high and low SAP subgroups, respectively (subjects with SAP level higher than 25.4 ± 2.8 mg/l were assigned into high SAP subgroup and those with SAP level less than 25.4 ± 2.8 mg/l were assigned into low SAP subgroup). Fig. 2 shows the mean time required for the complete healing of grafted wounds. The mean time required for complete wound healing was significantly shorter in patients with low SAP than those with high SAP in each group.
Fig. 1. SAP level distributions in burned patients according to BSA.
Fig. 3 shows the mean numbers of survived skin grafts stratified by SAP levels in each groups. There were significantly higher amounts of survived skin grafts in patients with low SAP than those with high SAP in G1 and G2 (both P b 0.05). Similar results were observed in G3 as well, although the difference was not statistically significant. Spearman's analyses were performed to test the correlation between the serum SAP level and the complete wound healing time as well as the mean numbers of survived skin grafts. The serum SAP levels negatively correlated with the complete wound healing time (r = −0.712, P b 0.001) and mean numbers of survived skin grafts (r = −0.662, P = 0.019). There was a positive correlation between mean numbers of survived skin grafts and the complete wound healing time (r = 0.825, P b 0.001). Logistic regression analysis was performed to investigate the independent variables associated with grafted skin survival and wound healing. The complete wound healing time was selected as dependent factor and other variables including age, SAP level and other commonly used clinical parameters, e.g., serum aspartate aminotransferase, serum alanine aminotransferase alkaline phosphatase, serum creatinine, and total bilirubin as independent factors. The result of logistic regression analysis showed that serum SAP levels (Hazard ratio = −2.68, 95% CI: −4.68 to −1.46, P = 0.013) and mean numbers of survived skin grafts (Hazard ratio = 3.47 95% CI: 1.37– 5.84, P b 0.001) were potent independent factors contributing to wound healing. The other clinical parameters as serum aspartate aminotransferase, serum alanine aminotransferase alkaline phosphatase, serum creatinine, and total bilirubin were not predictive factors for wounds healing (all P N 0.05).
Table 1 Clinical characteristics in cases and controls.
n Age (year) Sex (male, %) Smoker (%) SAP level (mg/L)
Case
Control
P
88 43.5 ± 6.7 48 (55.7%) 15 (17.0%) 25.4 ± 2.8
68 44.1 ± 5.9 39 (57.3%) 12 (17.6%) 24.5 ± 4.5
NS NS NS NS NS
Fig. 2. Mean complete healing time of grafted wound stratified by SAP levels in each group.
Y. Zhang et al. / Clinica Chimica Acta 412 (2011) 227–229
Fig. 3. Mean numbers of survived skin grafts stratified by SAP levels in each group.
229
skin graft, the numbers of survived grafts were studied as well. We found that the serum SAP levels negatively correlated with the complete wound healing time (r = −0.712, P b 0.001) and mean numbers of survived skin grafts (r = −0.662, P = 0.019). Additionally, both the serum SAP levels and mean numbers of survived skin grafts were potent independent factors contributing to wound healing. These results suggest that the serum SAP levels may be an easy detected predictor for the healing of burn wounds. We postulate that the different complete healing time may be due to the inhibition of the differentiation of monocytes into fibrocytes by SAP, however, in the current study, we did not explore the transformation of monocytes into fibrocytes and the local tissue fibrosis. This is a major limitation of our study. As this is a small-scale clinical study, the role of serum SAP in burn wound healing warrants further investigation in larger scale studies.
4. Discussion Acknowledgement In the present study, we found that serum SAP were negatively correlated to the number of survival skin grafts and the complete healing time. To the best of our knowledge, this is the first study regarding an association between the serum SAP levels and the burn wound healing and skin graft survival in patients with third degree burns receiving auto-skin graft. This finding hints that the serum SAP level may be helpful in predicting the prognosis of patients receiving auto-skin grafts. The functional role of fibrocytes in wound healing has been investigated previously. Mori et al. reported the presence of fibrocytes in healing wounds and the differentiation of fibrocytes into fibroblasts were observed [7]. Previous studies showed the transient presence of fibroblasts in early to mid phase wound tissue and fibroblasts has been proposed to exert a critical contractile force that is required to close wounds. Fibroblasts in the wound tissue are currently considered essential for the wound healing process [8–11]. SAP is a potent inhibitor to the differentiation of monocytes into fibrocytes and significantly reduces the myofibroblasts expressing alpha-smooth muscle actin [2]. The role of SAP in wound healing has been previous studied in animals. The addition of exogenous SAP delayed dermal wound healing in mice via increased inhibition of fibrocyte differentiation, and ultimately a decreased wound myofibroblast population, meanwhile SAP removal from wound fluid could potentially accelerate the healing of chronic, nonhealing wounds [5]. Reducing SAP levels at a wound site by an agarose/Ca(2+) dressings was reported to speed the healing of partial thickness wounds in pigs, suggesting that SAP depleting strategy may be beneficial for wound healing [6]. Our study is the first to investigate the role of SAP in wound healing process in burned patients. As all the patients received auto-
We thank Dr. Xiu Hua Li for her help in study design and we thank Dr. Bin Hu for his help in statistic analyses.
References [1] Moghazy AM, Adly OA, Abbas AH, Moati TA, Ali OS, Mohamed BA. Assessment of the relation between prealbumin serum level and healing of skin-grafted burn wounds. Burns 2010;36:495-500. [2] Pilling D, Buckley CD, Salmon M, Gomer RH. Inhibition of fibrocyte differentiation by serum amyloid P. J Immunol 2003;171:5537–46. [3] Castano AP, Lin SL, Surowy T, et al. Serum amyloid P inhibits fibrosis through Fc gamma R-dependent monocyte-macrophage regulation in vivo. Sci Transl Med 2009;1:5ra13. [4] Murray LA, Rosada R, Moreira AP, Joshi A, Kramer MS, Hesson DP, Argentieri RL, Mathai S, Gulati M, Herzog EL, Hogaboam CM. Serum amyloid P therapeutically attenuates murine bleomycin-induced pulmonary fibrosis via its effects on macrophages. PLoS One 2010;5:e9683. [5] Naik-Mathuria B, Pilling D, Crawford JRm, et al. Serum amyloid P inhibits dermal wound healing. Wound Repair Regen 2008;16:266–73. [6] Gomer RH, Pilling D, Kauvar LM, et al. A serum amyloid P-binding hydrogel speeds healing of partial thickness wounds in pigs. Wound Repair Regen 2009;17: 397–404. [7] Mori R, Kondo T, Ohshima T, Ishida Y, Mukaida N. Accelerated wound healing in tumor necrosis factor receptor p55-deficient mice with reduced leukocyte infiltration. FASEB J 2002;16:963–74. [8] Ishida Y, Gao JL, Murphy PM. Chemokine receptor CX3CR1 mediates skin wound healing by promoting macrophage and fibroblast accumulation and function. J Immunol 2008;180:569–79. [9] Fedakar-Senyucel M, Bingol-Kologlu M, Vargun R, et al. The effects of local and sustained release of fibroblast growth factor on wound healing in esophageal anastomoses. J Pediatr Surg 2008;43:290–5. [10] Watterson KR, Lanning DA, Diegelmann RF, Spiegel S. Regulation of fibroblast functions by lysophospholipid mediators: potential roles in wound healing. Wound Repair Regen 2007;15:607–16. [11] Darby IA, Hewitson TD. Fibroblast differentiation in wound healing and fibrosis. Int Rev Cytol 2007;257:143–79.
Contents lists available at ScienceDirect
Clinica Chimica Acta j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / c l i n c h i m
Role of serum amyloid P in skin graft survival and wound healing in burned patients receiving skin grafts Yi-ming Zhang a,1, Ya-dong Fang b,1, Yi-cheng Wang c, Shao-liang Wang a, Ze-yuan Lei a, Xiao-wei Liu a, Tong-chun Mao a, Dong-li Fan a,⁎ a
Department of Plastic and Cosmetic Surgery, Xinqiao Hospital, Third Military Medical University, Xinqiao Road, Sha Ping Ba District, Chongqing 400037, People's Republic of China State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Burn Research, Third Military Medical University, Southwest Hospital, Gaotanyan Street, Sha Ping Ba District, Chongqing 400038, People's Republic of China c Department of Plastic and Burn Surgery, Hospital of Chongqing Armed Police, Weiguo Road, Nan An District, Chongqing 400061, People's Republic of China b
a r t i c l e
i n f o
Article history: Received 2 June 2010 Received in revised form 12 August 2010 Accepted 10 September 2010 Available online 12 October 2010 Keywords: Serum amyloid P Skin graft Wound healing
a b s t r a c t Background: Recent studies in animal models suggest that serum amyloid P (SAP) can affect burn wound healing. However, the role of SAP in a clinical setting remains unknown. Methods: We enrolled 88 patients with third degree burn wounds. All the patients were candidates for autoskin graft procedure using stamp skin graft. The complete graft healing time and the number of survived grafts were recorded. Serum SAP levels were assessed 1 day before operation. Results: There was no significant difference in SAP level between controls and patients. There were no significant differences noted among the patients with different burn surface area. However, when the patients in each group were stratified by SAP levels, the mean complete healing time of grafted wound and the mean numbers of survived skin grafts were significantly different. Spearman's analyses showed that the serum SAP levels negatively correlated with the complete wound healing time and mean numbers of survived skin grafts. Logistic regression analysis showed that the serum SAP levels and mean numbers of survived skin grafts were potent independent factors contributing to wound healing. Conclusions: The results of this study suggest that the serum SAP levels may be an easy detected predictor for the healing of burn wounds. Crown Copyright © 2010 Published by Elsevier B.V. All rights reserved.
1. Introduction Skin grafting is a simple and common procedure widely used in burned patients to achieve wound closure. The effect of this procedure is mainly dependent on the survival of the grafted skin. A recent study showed that the serum marker, prealbumin, is a sensitive predictor for the graft healing in burned patients [1]. As burn wound healing involves the proliferation and differentiation of fibroblasts and the deposition of extracellular matrix, whether factors associated with fibrotic proliferation and differentiation determine the wound healing process attracts our interest. Serum amyloid P (SAP) is a plasma glycoprotein which was first identified as a protein component of systemic amyloid deposits. SAP is also a potent regulator of organic fibrosis by inhibiting the differentiation of monocytes into fibrocytes [2–4]. Relatively small changes in the circulating levels of SAP may have an important effect on the fibrotic process in vivo. An animal study showed that SAP Abbreviations: SAP, Serum amyloid P; BSA, Burn surface area. ⁎ Corresponding author. Tel.: + 86 023 68755302; fax: +86 023 68755306. E-mail addresses: [email protected], [email protected] (D. Fan). 1 The authors contributed equally to this paper.
delays normal murine dermal wound healing due to increased inhibition of fibrocyte differentiation depleting SAP at a wound site can speed the wound healing and reducing serum amyloid P by a binding hydrogel speeds healing of partial thickness wounds in pigs. All these observations in animal models strongly suggest that SAP [5,6] is an active factor associated with wound healing. To date, there is no clinical study regarding the role of SAP in wound healing in burned patients. In the present study, we explored the association between the serum level of SAP and the wound healing of in burned patients subject to auto-skin graft. 2. Methods 2.1. Patients From Feb 2008 to Aug 2009, we enrolled 88 patients with third degree burn wounds, among which 49 were female and 39 were male with the average age at 43.8 ± 8.1 year. The area of third degree burn wound varied from 5% to 75%. The burn wounds were located in the body trunk and four extremities. According to the burn surface area (BSA), all patients were divided into three groups, namely, G1 (BSA 5– 25%, n = 26), G2 (BSA 25–50%, n = 42) and G3 (BSA 50%–75%, n = 20).
0009-8981/$ – see front matter. Crown Copyright © 2010 Published by Elsevier B.V. All rights reserved. doi:10.1016/j.cca.2010.09.036
228
Y. Zhang et al. / Clinica Chimica Acta 412 (2011) 227–229
All the patients were candidates for auto-skin graft procedure using stamp skin graft. All the patients were on regular oral feeding (no special diet or supplements). The skin grafts were observed daily after operation by 2 burn surgeons to evaluate the wounds healing. Complete graft healing was considered when graft take was more than 90% of graft size and the complete healing time (days) were recorded. The stamp skin grafts tightly attached to the host burn wound bed were considered survival and their number/100 cm2 were recorded. The observation was performed in 3 independent grafted wounds in each patient and the average survival number was calculated. Patients with head and neck burns, and those with connective tissue disease, autoimmune diseases and diabetic mellitus were excluded from the study. Sixty-eight sex and age matched healthy controls were enrolled in this study. 2.2. Serum SAP detection Serum SAP levels were assessed 1 day before operation by ELISA method as follows: microtitre plates were coated in 0.01 mol/l PBS with 2 mg/ml of a monoclonal antibody directed against SAP (1:1500, Santa Cruz Biotechnology, Santa Cruz, CA) for 1 h. After washing, sera were added starting at a 250-fold dilution, with a further fourfold dilution in 0.05 mol/l Tris, 0.3 mol/l NaCl, 1% BSA, and 0.05% Tween-20 for 1 h. A reference serum was added as a positive control. Monoclonal antibody conjugated with horseradish peroxidase directed against human SAP (1:2000, Santa Cruz Biotechnology) was applied for 30 min using an ELISA shaker in the dark. 2.3. Statistical analysis Data were expressed as mean value and SD. Statistical significance of the correlation was determined by Spearman's coefficient. Student's t test and χ2 test were used to evaluate significance in clinical characteristics between the two groups. A p b 0.05 was considered significant. 3. Results Table 1 summarized the clinical characteristics in cases and controls. There are no significant differences in age, sex, prevalence and the percentage of smokers between cases and controls (all P = NS). The mean SAP level in controls was 24.5 ± 4.5 mg/l, while in patients was 25.4 ± 2.8 mg/l, no significant differences were observed (P = NS). Fig. 1 shows the SAP level distribution in the burned patients according to their BSA. There were no significant differences noted among the G1, G2 and G3 groups. The overall mean SAP level in all patients was 25.4± 2.8 mg/l. According to the overall mean SAP level, all the patients in each group were stratified into high and low SAP subgroups, respectively (subjects with SAP level higher than 25.4 ± 2.8 mg/l were assigned into high SAP subgroup and those with SAP level less than 25.4 ± 2.8 mg/l were assigned into low SAP subgroup). Fig. 2 shows the mean time required for the complete healing of grafted wounds. The mean time required for complete wound healing was significantly shorter in patients with low SAP than those with high SAP in each group.
Fig. 1. SAP level distributions in burned patients according to BSA.
Fig. 3 shows the mean numbers of survived skin grafts stratified by SAP levels in each groups. There were significantly higher amounts of survived skin grafts in patients with low SAP than those with high SAP in G1 and G2 (both P b 0.05). Similar results were observed in G3 as well, although the difference was not statistically significant. Spearman's analyses were performed to test the correlation between the serum SAP level and the complete wound healing time as well as the mean numbers of survived skin grafts. The serum SAP levels negatively correlated with the complete wound healing time (r = −0.712, P b 0.001) and mean numbers of survived skin grafts (r = −0.662, P = 0.019). There was a positive correlation between mean numbers of survived skin grafts and the complete wound healing time (r = 0.825, P b 0.001). Logistic regression analysis was performed to investigate the independent variables associated with grafted skin survival and wound healing. The complete wound healing time was selected as dependent factor and other variables including age, SAP level and other commonly used clinical parameters, e.g., serum aspartate aminotransferase, serum alanine aminotransferase alkaline phosphatase, serum creatinine, and total bilirubin as independent factors. The result of logistic regression analysis showed that serum SAP levels (Hazard ratio = −2.68, 95% CI: −4.68 to −1.46, P = 0.013) and mean numbers of survived skin grafts (Hazard ratio = 3.47 95% CI: 1.37– 5.84, P b 0.001) were potent independent factors contributing to wound healing. The other clinical parameters as serum aspartate aminotransferase, serum alanine aminotransferase alkaline phosphatase, serum creatinine, and total bilirubin were not predictive factors for wounds healing (all P N 0.05).
Table 1 Clinical characteristics in cases and controls.
n Age (year) Sex (male, %) Smoker (%) SAP level (mg/L)
Case
Control
P
88 43.5 ± 6.7 48 (55.7%) 15 (17.0%) 25.4 ± 2.8
68 44.1 ± 5.9 39 (57.3%) 12 (17.6%) 24.5 ± 4.5
NS NS NS NS NS
Fig. 2. Mean complete healing time of grafted wound stratified by SAP levels in each group.
Y. Zhang et al. / Clinica Chimica Acta 412 (2011) 227–229
Fig. 3. Mean numbers of survived skin grafts stratified by SAP levels in each group.
229
skin graft, the numbers of survived grafts were studied as well. We found that the serum SAP levels negatively correlated with the complete wound healing time (r = −0.712, P b 0.001) and mean numbers of survived skin grafts (r = −0.662, P = 0.019). Additionally, both the serum SAP levels and mean numbers of survived skin grafts were potent independent factors contributing to wound healing. These results suggest that the serum SAP levels may be an easy detected predictor for the healing of burn wounds. We postulate that the different complete healing time may be due to the inhibition of the differentiation of monocytes into fibrocytes by SAP, however, in the current study, we did not explore the transformation of monocytes into fibrocytes and the local tissue fibrosis. This is a major limitation of our study. As this is a small-scale clinical study, the role of serum SAP in burn wound healing warrants further investigation in larger scale studies.
4. Discussion Acknowledgement In the present study, we found that serum SAP were negatively correlated to the number of survival skin grafts and the complete healing time. To the best of our knowledge, this is the first study regarding an association between the serum SAP levels and the burn wound healing and skin graft survival in patients with third degree burns receiving auto-skin graft. This finding hints that the serum SAP level may be helpful in predicting the prognosis of patients receiving auto-skin grafts. The functional role of fibrocytes in wound healing has been investigated previously. Mori et al. reported the presence of fibrocytes in healing wounds and the differentiation of fibrocytes into fibroblasts were observed [7]. Previous studies showed the transient presence of fibroblasts in early to mid phase wound tissue and fibroblasts has been proposed to exert a critical contractile force that is required to close wounds. Fibroblasts in the wound tissue are currently considered essential for the wound healing process [8–11]. SAP is a potent inhibitor to the differentiation of monocytes into fibrocytes and significantly reduces the myofibroblasts expressing alpha-smooth muscle actin [2]. The role of SAP in wound healing has been previous studied in animals. The addition of exogenous SAP delayed dermal wound healing in mice via increased inhibition of fibrocyte differentiation, and ultimately a decreased wound myofibroblast population, meanwhile SAP removal from wound fluid could potentially accelerate the healing of chronic, nonhealing wounds [5]. Reducing SAP levels at a wound site by an agarose/Ca(2+) dressings was reported to speed the healing of partial thickness wounds in pigs, suggesting that SAP depleting strategy may be beneficial for wound healing [6]. Our study is the first to investigate the role of SAP in wound healing process in burned patients. As all the patients received auto-
We thank Dr. Xiu Hua Li for her help in study design and we thank Dr. Bin Hu for his help in statistic analyses.
References [1] Moghazy AM, Adly OA, Abbas AH, Moati TA, Ali OS, Mohamed BA. Assessment of the relation between prealbumin serum level and healing of skin-grafted burn wounds. Burns 2010;36:495-500. [2] Pilling D, Buckley CD, Salmon M, Gomer RH. Inhibition of fibrocyte differentiation by serum amyloid P. J Immunol 2003;171:5537–46. [3] Castano AP, Lin SL, Surowy T, et al. Serum amyloid P inhibits fibrosis through Fc gamma R-dependent monocyte-macrophage regulation in vivo. Sci Transl Med 2009;1:5ra13. [4] Murray LA, Rosada R, Moreira AP, Joshi A, Kramer MS, Hesson DP, Argentieri RL, Mathai S, Gulati M, Herzog EL, Hogaboam CM. Serum amyloid P therapeutically attenuates murine bleomycin-induced pulmonary fibrosis via its effects on macrophages. PLoS One 2010;5:e9683. [5] Naik-Mathuria B, Pilling D, Crawford JRm, et al. Serum amyloid P inhibits dermal wound healing. Wound Repair Regen 2008;16:266–73. [6] Gomer RH, Pilling D, Kauvar LM, et al. A serum amyloid P-binding hydrogel speeds healing of partial thickness wounds in pigs. Wound Repair Regen 2009;17: 397–404. [7] Mori R, Kondo T, Ohshima T, Ishida Y, Mukaida N. Accelerated wound healing in tumor necrosis factor receptor p55-deficient mice with reduced leukocyte infiltration. FASEB J 2002;16:963–74. [8] Ishida Y, Gao JL, Murphy PM. Chemokine receptor CX3CR1 mediates skin wound healing by promoting macrophage and fibroblast accumulation and function. J Immunol 2008;180:569–79. [9] Fedakar-Senyucel M, Bingol-Kologlu M, Vargun R, et al. The effects of local and sustained release of fibroblast growth factor on wound healing in esophageal anastomoses. J Pediatr Surg 2008;43:290–5. [10] Watterson KR, Lanning DA, Diegelmann RF, Spiegel S. Regulation of fibroblast functions by lysophospholipid mediators: potential roles in wound healing. Wound Repair Regen 2007;15:607–16. [11] Darby IA, Hewitson TD. Fibroblast differentiation in wound healing and fibrosis. Int Rev Cytol 2007;257:143–79.