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Lymphocytosis-promoting factor of Bordetella pertussis alters mononuclear phagocyte circulation and response to
Abstract:
Previous results from our laboratory demonstrated that purified lymphocytosis-promoting factor (LPF), a protein toxin from Bordetella pertussis, inhibited the migration of murine macrophages in vitro. The current study examined the in vivo effects of LPF on mononuclear phagocyte circulation and response to an inflammatory stimulus. Intravenous injection of mice with 200 ng of LPF produced a prolonged monocytosis which peaked with a fivefold increase on day 5 after injection. LPF (200 ng) also inhibited by more than 75% the increase in peritoneal inflammatory macrophages induced by intraperitoneal injection of thioglycolate broth, phytohemagglutinin, or paraffin oil. The inhibition was significant when thioglycolate was given 1 h or 2 or 4 days after LPF but not when thioglycolate was given 2 or 4 days before LPF. The LPF-induced monocytosis on day 5 after injections was not altered by the intraperitoneal injection of thioglycolate broth. The leukocytosis-promoting and macrophage-inhibiting properties of LPF were the same in N:NIH(S) and C3H/HeJ mice. Treatments of LPF that reduced the leukocytosis-promoting effect of LPF also reduced the ability of LPF to inhibit the macrophage response. LPF doses sufficient to induce leukocytosis (greater than or equal to 25 ng) significantly inhibited the thioglycolate-induced increase in peritoneal macrophages. The results indicate that coincident with an LPF-induced monocytosis is a reduction in the number of mononuclear phagocytes at a site of inflammation. An in vivo inhibition of mononuclear phagocyte migration would explain both effects of LPF and is consistent with the in vitro inhibition of macrophage migration by LPF.
Insights
Bordetella pertussis lymphocytosis-promoting factor (LPF) causes increased white blood cells and reduces macrophage accumulation at inflammation sites in mice. This suggests LPF inhibits mononuclear phagocyte migration in vivo.
Area of Science:
- Immunology
- Microbiology
Background:
- Previous studies showed Bordetella pertussis lymphocytosis-promoting factor (LPF) inhibits macrophage migration in vitro.
- The in vivo effects of LPF on mononuclear phagocyte circulation and inflammatory responses were investigated.
Purpose of the Study:
- To determine the in vivo impact of LPF on mouse immune cell circulation.
- To assess LPF's effect on the accumulation of inflammatory macrophages.
Main Methods:
- Mice received intravenous injections of LPF.
- Peritoneal macrophages were induced using thioglycolate broth, phytohemagglutinin, or paraffin oil.
- LPF's effects on monocytosis and macrophage accumulation were quantified.
Main Results:
- LPF induced a significant, prolonged monocytosis peaking at fivefold increase on day 5.
- LPF inhibited inflammatory macrophage increases by over 75% when administered before inflammatory stimuli.
- LPF's leukocytosis-promoting and macrophage-inhibiting effects were dose-dependent and linked.
Conclusions:
- LPF induces monocytosis while simultaneously reducing mononuclear phagocyte accumulation at inflammatory sites.
- These findings suggest LPF inhibits mononuclear phagocyte migration in vivo.
- The in vivo results align with previously observed in vitro inhibition of macrophage migration by LPF.