Requirements for alpha d in IgG immune complex-induced rat lung injury.
Alpha d is a newly cloned adhesion molecule that forms a heterodimer with CD18. The requirement for alpha d in IgG immune complex-induced lung injury in rats has been evaluated by the use of blocking polyclonal and monoclonal antibodies to rat alpha d. Using whole lung extracts, Northern and Western blot analyses have revealed up-regulation of mRNA and alpha d protein in inflamed lungs. Immunostaining has revealed the presence of alpha d in lung tissue and in alveolar macrophages as early as 1 h after initiation of the inflammatory reaction. When polyclonal rabbit Ab to rat alpha d was coinstilled into lung together with Ab to BSA, lung injury (as determined by leakage of [125I]albumin into lung parenchyma) was significantly diminished. In parallel, there was reduced accumulation of neutrophils recoverable in bronchoalveolar lavage (BAL) fluids. These findings were associated with reduced levels of TNF-alpha as well as NO2-/NO3- in BAL fluids. A hamster mAb to rat alpha d was also protective in this lung injury model. Anti-alpha d inhibited in vitro production of NO2-/NO3- by rat alveolar macrophages (stimulated with LPS and IFN-gamma) by approximately 60%. These data suggest that, in the lung inflammatory model employed, alpha d up-regulation occurs in lung macrophages and is necessary for expression of TNF-alpha, recruitment of neutrophils, and full development of lung injury.
Shanley
T P
TP
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602, USA.
Warner
R L
RL
Crouch
L D
LD
Dietsch
G N
GN
Clark
D L
DL
O'Brien
M M
MM
Gallatin
W M
WM
Ward
P A
PA
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D018845:CD11 Antigens / Q000302:isolation & purification; D005786:Gene Expression Regulation / Q000276:immunology; D007105:Immune Complex Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007106:Immune Sera / Q000008:administration & dosage; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000633:toxicity*; D007322:Instillation, Drug; D039001:Integrin alpha Chains; D016023:Integrins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D007958:Leukocyte Count; D008168:Lung / Q000737:chemistry / Q000276:immunology* / Q000473:pathology; D008262:Macrophage Activation / Q000276:immunology; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D009566:Nitrates / Q000037:antagonists & inhibitors / Q000378:metabolism; D009573:Nitrites / Q000037:antagonists & inhibitors / Q000378:metabolism; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D016024:Receptors, Cytoadhesin; D013194:Staining and Labeling; D014132:Trachea; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D018845:CD11 Antigens; C406812:ITGAD protein, human; D007106:Immune Sera; D007074:Immunoglobulin G; D039001:Integrin alpha Chains; D016023:Integrins; D009566:Nitrates; D009573:Nitrites; D012333:RNA, Messenger; D016024:Receptors, Cytoadhesin; D014409:Tumor Necrosis Factor-alpha