Effect of genetic variation on induced neutrophilia in mice

Abstract

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.

Genetic variation in neutrophil accumulation in mice is not mediated through immigrant regulatory cells

“…inoculation of IL-la resulted in a neutrophil response at 18 h p.i. in both strains which was within the range known to be induced by BT in BALB/c mice [8], but a macrophage response comparable to B.IO mice (see Fig. Id).…”

“…Mice show genetically determined variation in the acute peritoneal neutrophilia elicited by i.p. injection of a sterile irritant [8]. This variation could reflect strain-dependent differences in the kinetics and/or cytokine production of three major transitory cell populations within the peritoneal cavity -T cells, macrophages and mast cells all of which could potentially regulate neutrophil influx.…”

“…We have described [8] a murine model of genetic variation in neutrophil accumulation. Mice challenged with intra-peritoneal injection of a sterile irritant (Brewer thioglycollate) behaved as low (BALB/c) or high responders (C57BI/10 [B.IO]).…”

Bacterial Nucleotidyl Cyclase Inhibits the Host Innate Immune Response by Suppressing TAK1 Activation

“…Sufficient recruitment of neutrophils to the site of infection was essential for clearance of P. aeruginosa. BALB/c mice have a lower inflammatory response than mice with a C57BL background and decreased accumulation of neutrophils upon bacterial stimulation (44,45). In ΔexoY strain-infected BALB/c mice, recruitment of neutrophils to the lungs may be blunted compared with that of C57BL/6 mice infected with the ΔexoY strain.…”