REQUIREMENTS FOR ALPHA-D IN IGG IMMUNE COMPLEX-INDUCED RAT LUNG INJURY

alpha d is a newly cloned adhesion molecule that forms a heterodimer w ith CD18, The requirement for alpha d in IgG immune complex-induced lu ng 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 th e presence of alpha d in lung tissue and in alveolar macrophages as ea rly as 1 h after initiation of the inflammatory reaction, When polyclo nal rabbit Ab to rat alpha d was coinstilled into lung together with A b to BSA, lung injury (as determined by leakage of [(125)l]albumin int o lung parenchyma) was significantly diminished, In parallel, there wa s reduced accumulation of neutrophils recoverable in bronchoalveolar l avage (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 i nhibited in vitro production of NO2-/NO3- by rat alveolar macrophages (stimulated with LPS and IFN-gamma) by approximately 60%, These data s uggest that, in the lung inflammatory model employed, alpha d up-regul ation occurs in lung macrophages and is necessary for expression of TN F-alpha, recruitment of neutrophils, and full development of lung inju ry.