Am. J. Respir. Cell Mol. Biol., Volume 20, Number 3, March, 1999 448-457

The Role of 4 (CD49d) and 2 (CD18) Integrins in Eosinophil and Neutrophil Migration to Allergic Lung Inflammation in the Brown Norway Rat

Thorsten Schneider, Thomas B. Issekutz, and Andrew C. Issekutz

Departments of Pediatrics and Microbiology-Immunology, Dalhousie University, Halifax, Nova Scotia, Canada

We investigated the role of 2 (CD18) and 4 (CD49d) integrins in eosinophil and neutrophil recruitment to lung parenchyma and bronchoalveolar lavage fluid (BALF) of allergen-challenged Brown Norway (BN) rats. Challenge of sensitized BN rats with ovalbumin induced an eosinophil- and neutrophil-rich infiltrate in BALF at 24 h, accompanied by an increase in BALF protein content. Treatment with either the TA-2 monoclonal antibody (mAb) against 4 (as an F[ab']₂ fragment) or the WT.3 mAb against 2 integrin significantly reduced eosinophil and neutrophil accumulation in BALF by 54 to 66% and eosinophil accumulation in the parenchyma by 48%. A significant difference in effect was observed between mAb TA-2 in intact immunoglobulin G or F(ab)₂ form. Combined treatment with mAbs WT.3 plus TA-2 (F[ab]₂) virtually abolished eosinophil accumulation in BALF and in the parenchyma, and reduced neutrophil accumulation in BALF by 91%. In contrast, neutrophil accumulation in the lung was not inhibited by these mAb treatments. The increase in BALF protein concentration was significantly inhibited by TA-2 (by 40%) and by WT.3 plus TA-2 in combination (71% inhibition). We conclude that eosinophil and neutrophil migration into the air space in allergic lung inflammation is partially CD18 (2)- and CD49d (4)- dependent and that 4 integrins mediate essentially all of the CD18-independent migration. Similarly, eosinophil accumulation in the parenchyma is completely 4 and CD18 (2) integrin-dependent. In marked contrast, neutrophil accumulation in the lung in this allergen model can occur independently of both 4 and 2 integrins.

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