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.