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43 Pulmonary macrophage metabolism of M. Faeni in a model of hypersensitivity pneumonitis
41
THE EFFECT OF BRONCHOALVEOLAR LAVAGE CELLS ON B-LYMPHOCYTE FUNCTION.
J Morgan
PM,
43
D Weissman
MD, C Daul MD PhD, R deShazo MD and D Banks MD. New Orleans, Louisiana.
Schmitt, Fark Schuyler,'M.Dr-~~-and, onlo. Pulmonary histologic abnormaiitii,s ;es.~lvt= despite continuing intratrachea: ti: .) injections of M. faeni in a rabbit m::di~l 0:' hypersensitivity pneumonitis iHI') (AhRiI 128:2071, 1983). WC tested t-112 iacputl esis iiiat increased efficiency of alveolar. mtc-:opbape (AM) catabolism of X. faeni was as:;o<,iate.: ;giti: these changes. We examined in vitro mttabn! isn! of labelled particulate M. faeni b-2 ia~,g< ceils from naive and M. faeni treated (5, t ‘init II i.t. injections) rabbits, We measure: i!re amount of label in the cell pellet; in the .,upernatant; and the proportion of the supernatan; (Itat was TCA precipitable after cultur(5 for \,J.'~,h,i8,24 and 48 hours. Change of the amount of l.lbel in tne pellet and supernatant was dependent upon mime. viable cells, temperature, and the presence oi AM and was not altered by puromycin. AM from M. faeni treated rabhic-, wrre slightly more effective in transport of label from pellet to supernatant over the "irst 4 hours of culture, but not thereafter. There was no difference between AM from rabbits challenged of the 5, 7, and II times or in the percent supernatant label that was TCA prrripitnble. We conclude that resolutfon of n~jlmnnarv histologic abnormalities in this modf!l of HP is not associated with evidence of enhanced AM particulate M. faeni catabolism.
Differences
in bronchoalveolar lavage fluid (Ig) content exist between and non-smokers (NS). We therefore the effect of NS and S bronchoalveolar
immunoglobulin smokers (S)
compared lavage cells (BALC) OII IgA and IgG production by autologous monocyte-depleted (
42
ALVEOLARMACRGPHAGE ACTLVATLON--DOES NOT SUPPRr;SS LUk& LM~~UN~X,OGLC BExCTIVLTY. -Mark R Schuyler M.D., Cleveland, Ohio. Determinants of lung immunologic response to antigens are not known, but could include alveolar macrophage (AM) activation. We tested this hypothesis by activating macrophages (intratracheal (i.t.) rt. faeni) and then exposing rabbits to i.t. bovine serum albumin (PSA). We examined serum and lavage fluid antiaSA IgG antibody levels (radioimswnoassay) and hUg and hilar node %A (.01-l n&al) and Con A induced lymphocyte proliferation 21 days after BSA administration. M. faeni adrainistered i.t. increased the numhsr of AM. These AM were activated (increased phagocytosis of EgG coated particles). Naive rabbits exhibited neither anti-gSa antibody in serum and lavage fluid nor HSA induced lymphocyte proliferation. USA treated animals had antibody in both serum and lavage fluid and &A induced lymphocyte proliferation. I coatpared the results from 4 groups of animals (i.t. administration of either normal saline or 50 ag M. faeni and later administration of either i.t. or 1.m. USA). L found no difference in the amount of antibody in either lavage fluid or serum or in antigen or Con A induced lung and hilar node lymphocyte proliferation in these 4 groups. I conclude that macrophage activation does not alter the ability of the lung to respond to intratracheal antigen.
PULMONARY MACROPHAGEMETABOLISM OF MI. -. BU%VJL IN ____--_-_.-.._-
A MODELOF HYPERSENSITIVITY PNECWONITIS.David -.____.--.c__ --i-7
44
115
AN ANIMAL MODELOF HYPERSENSITIVITY F~U~~ITIS. ;4c:;FsMJ;, Calvanico, Ph.D. and Robert H. 1 , . ., Mtlwaukee, Wiscanstn These studies are part of our ongoing research into the nature of i~ol~gic mechanisms of chronic granulomatous inf'latwnation of alveolar and interstitial tissue associated with hypersensitivity pnetnnonitis (HP). R&bits which have been immunized and insufflated daily with a protein antigen develop pulmonary inflatnnation in 1 to 2 weeks. This inflaeaeation however rapidly wanes and after 4 to 6 weeks of continued insufflation the lung returns to normal. This course is believed to simulate the response of a normal lung to inhaled allergens. In order to elucidate the pathogenesis of HP we have initiated studies on the nature of the unresponsive state following the inflammatory phase in these animals. We attempted to determine if the lung could respond to a second antigenic challenge with a protein unrelated to the one causing the initial inflammatory response. We used histopathology and the release of plasminogen activator from the alveolar macrophage as indicators of pulnonary SnflaRmation. Our results showed that for 30 weeks following the initial challenge with aerosolized antigen, the rabbit was refractory to a second inflaam!atory course with a new (or After this period, the the s&ma) antigen. rabbits became susceptible to a second inflammation with the new antigen but ware still unresponsive to the initial antigen. We concluded that the post-inflammatory period is normally characterized by a period of anti,gen nonspecific so pression followed by a period of antigen specif Pc suppression.
THE EFFECT OF BRONCHOALVEOLAR LAVAGE CELLS ON B-LYMPHOCYTE FUNCTION.
J Morgan
PM,
43
D Weissman
MD, C Daul MD PhD, R deShazo MD and D Banks MD. New Orleans, Louisiana.
Schmitt, Fark Schuyler,'M.Dr-~~-and, onlo. Pulmonary histologic abnormaiitii,s ;es.~lvt= despite continuing intratrachea: ti: .) injections of M. faeni in a rabbit m::di~l 0:' hypersensitivity pneumonitis iHI') (AhRiI 128:2071, 1983). WC tested t-112 iacputl esis iiiat increased efficiency of alveolar. mtc-:opbape (AM) catabolism of X. faeni was as:;o<,iate.: ;giti: these changes. We examined in vitro mttabn! isn! of labelled particulate M. faeni b-2 ia~,g< ceils from naive and M. faeni treated (5, t ‘init II i.t. injections) rabbits, We measure: i!re amount of label in the cell pellet; in the .,upernatant; and the proportion of the supernatan; (Itat was TCA precipitable after cultur(5 for \,J.'~,h,i8,24 and 48 hours. Change of the amount of l.lbel in tne pellet and supernatant was dependent upon mime. viable cells, temperature, and the presence oi AM and was not altered by puromycin. AM from M. faeni treated rabhic-, wrre slightly more effective in transport of label from pellet to supernatant over the "irst 4 hours of culture, but not thereafter. There was no difference between AM from rabbits challenged of the 5, 7, and II times or in the percent supernatant label that was TCA prrripitnble. We conclude that resolutfon of n~jlmnnarv histologic abnormalities in this modf!l of HP is not associated with evidence of enhanced AM particulate M. faeni catabolism.
Differences
in bronchoalveolar lavage fluid (Ig) content exist between and non-smokers (NS). We therefore the effect of NS and S bronchoalveolar
immunoglobulin smokers (S)
compared lavage cells (BALC) OII IgA and IgG production by autologous monocyte-depleted (
42
ALVEOLARMACRGPHAGE ACTLVATLON--DOES NOT SUPPRr;SS LUk& LM~~UN~X,OGLC BExCTIVLTY. -Mark R Schuyler M.D., Cleveland, Ohio. Determinants of lung immunologic response to antigens are not known, but could include alveolar macrophage (AM) activation. We tested this hypothesis by activating macrophages (intratracheal (i.t.) rt. faeni) and then exposing rabbits to i.t. bovine serum albumin (PSA). We examined serum and lavage fluid antiaSA IgG antibody levels (radioimswnoassay) and hUg and hilar node %A (.01-l n&al) and Con A induced lymphocyte proliferation 21 days after BSA administration. M. faeni adrainistered i.t. increased the numhsr of AM. These AM were activated (increased phagocytosis of EgG coated particles). Naive rabbits exhibited neither anti-gSa antibody in serum and lavage fluid nor HSA induced lymphocyte proliferation. USA treated animals had antibody in both serum and lavage fluid and &A induced lymphocyte proliferation. I coatpared the results from 4 groups of animals (i.t. administration of either normal saline or 50 ag M. faeni and later administration of either i.t. or 1.m. USA). L found no difference in the amount of antibody in either lavage fluid or serum or in antigen or Con A induced lung and hilar node lymphocyte proliferation in these 4 groups. I conclude that macrophage activation does not alter the ability of the lung to respond to intratracheal antigen.
PULMONARY MACROPHAGEMETABOLISM OF MI. -. BU%VJL IN ____--_-_.-.._-
A MODELOF HYPERSENSITIVITY PNECWONITIS.David -.____.--.c__ --i-7
44
115
AN ANIMAL MODELOF HYPERSENSITIVITY F~U~~ITIS. ;4c:;FsMJ;, Calvanico, Ph.D. and Robert H. 1 , . ., Mtlwaukee, Wiscanstn These studies are part of our ongoing research into the nature of i~ol~gic mechanisms of chronic granulomatous inf'latwnation of alveolar and interstitial tissue associated with hypersensitivity pnetnnonitis (HP). R&bits which have been immunized and insufflated daily with a protein antigen develop pulmonary inflatnnation in 1 to 2 weeks. This inflaeaeation however rapidly wanes and after 4 to 6 weeks of continued insufflation the lung returns to normal. This course is believed to simulate the response of a normal lung to inhaled allergens. In order to elucidate the pathogenesis of HP we have initiated studies on the nature of the unresponsive state following the inflammatory phase in these animals. We attempted to determine if the lung could respond to a second antigenic challenge with a protein unrelated to the one causing the initial inflammatory response. We used histopathology and the release of plasminogen activator from the alveolar macrophage as indicators of pulnonary SnflaRmation. Our results showed that for 30 weeks following the initial challenge with aerosolized antigen, the rabbit was refractory to a second inflaam!atory course with a new (or After this period, the the s&ma) antigen. rabbits became susceptible to a second inflammation with the new antigen but ware still unresponsive to the initial antigen. We concluded that the post-inflammatory period is normally characterized by a period of anti,gen nonspecific so pression followed by a period of antigen specif Pc suppression.