Effects of CD18 deficiency on the emigration of murine neutrophils during pneumonia

We hypothesized that CD18 deficiency would impair the ability of neutrophil s to emigrate from pulmonary blood vessels during certain pneumonias. To di rectly compare the abilities of wild-type (WT) and CD18-deficient neutrophi ls to emigrate, mice with both types of leukocytes in their blood were gene rated by reconstituting the hemopoietic systems of lethally irradiated C57B L/6 mice with mixtures of fetal liver cells from WT and CD18-deficient mice . Percentages of CD18-deficient neutrophils in the circulating and emigrate d pools were compared during experimental pneumonias, Similar percentages w ere observed in the blood and bronchoalveolar lavage fluid 6 or 24 h after intratracheal instillation of Streptococcus pneumoniae, demonstrating that no site on the CD18 molecule was required for either its adhesive or its si gnaling functions during neutrophil emigration. However, 6 h after instilla tion of Escherichia coli LPS or Pseudomonas aeruginosa, the percentage of C D18-deficient neutrophils in the bronchoalveolar lavage fluid was only abou t one-fourth of that observed in the blood. This difference persisted for a t least 24 h after instillation of E, coli LPS, Thus, neutrophil emigration elicited by the Gram-negative stimuli E. coli LPS or P, aeruginosa was com promised by deficiency of CD18, These data, based on comparing WT and gene- targeted CD18-deficient neutrophils within the same animals, provide eviden ce for molecular pathways regulating neutrophil emigration, which could not be appreciated in previous studies with pharmacological blockade or geneti c deficiency of CD18.