Effect of genetic variation on induced neutrophilia in mice

Mice from a variety of strains were injected with a sterile irritant (Brewer's thioglycolate) and killed bacteria (Staphylococcus aureus, Staphylococcus epidermidis, or Escherichia coli) to determine their effect on accumulation of neutrophils in the peritoneal cavity. Peak accumulation occurred around 15 h postinjection and showed significant strain-related variation. C57BL/10 mice were identified as having a high-responder phenotype and BALB/c mice a low-responder phenotype. Inheritance of the high-responder phenotype followed simple Mendelian genetics: (BALB/c x C57BL/10)F1 mice were found to be more responsive than either parental phenotype. Major histocompatibility complex H-2d haplotype was found to convey an augmented neutrophil response in conjunction with B10 background high-responder genes (B10.D2/n) but the H-2d haplotype per se was not the only factor in determining high responsiveness. Gram-positive and gram-negative bacteria appeared to activate different immune mechanisms. Both gram-negative bacteria and lipopolysaccharides (LPS) induced a response similar to, but less potent than, that induced by Brewer's thioglycollate. Neutralization of the LPS content of Brewer's thioglycolate abrogated the response.