The role of Mac-1 (CD11b/CD18) in antigen-induced airway eosinophilia in mice

Mac-1 (CD11b/CD18) is an important adhesion molecule involved in the migrat ion of leukocytes, cell signaling, and subsequent secretory responses. Its precise role in eosinophil recruitment and activation in vivo is not entire ly clear. We wished to directly examine the role of Mac-1 in eosinophil mig ration in a murine model of allergic pulmonary inflammation. Briefly, wild- type (C57B1/6) and Mac-1-deficient/knockout (Mac-1 KO) mice were intraperit oneally sensitized with ovalbumin (OVA) and alum (AlOH) on Days 0 and 14, a nd intranasally challenged with OVA either once on Day 14 or five times on Days 14 and 25 through 28. Control animals were challenged with saline. Bro nchial hyperresponsiveness was measured, bronchoalveolar lavage (BAL) fluid was collected, and lungs were harvested for histology 24 h after the last challenge. The data demonstrate that wild-type (WT) mice do not respond to one OVA challenge but do develop bronchial hyperreactivity and airway and t issue eosinophilia after five OVA challenges. Conversely, Mac-1 KO mice dev elop significant airway eosinophilia after one OVA challenge, and the degre e of airway inflammation is comparable to that observed in allergic WT mice after five challenges. In Mac-1 KO mice, after five challenges, bronchial hyperreactivity and airway inflammation was significantly enhanced compared with their wildtype counterparts. Administration of an anti-Mac-1 antibody to WT mice, before each of five intranasal OVA challenges, significantly r educes the airway eosinophilia but has no effect on tissue eosinophilia or bronchial hyperresponsiveness. Intravenous injection of interleukin-5 induc ed a significant blood eosinophilia in both WT and Mac-1 KO mice. Intranasa l eotaxin administration induced similar levels of eosinophil migration int o the lung tissues and airways of both WT and Mac-1 KO mice. In conclusion, Mac-l-deficient mice develop enhanced eosinophilic inflammation in the lun g in response to allergic antigen challenge.