| Autor: |
Schönlau, Frank, Schlesiger, Christian, Ehrehen, Jan, Grabbe, Stephan, Sorg, Clemens, Sunderkötter, Cord |
| Zdroj: |
Journal of Leukocyte Biology; May 2003, Vol. 73 Issue: 5 p564-573, 10p |
| Abstrakt: |
Mice with a naturally occurring Csfmop/Csfmop(op/op) gene mutation lack functional macrophage‐colony stimulating factor (M‐CSF) and are deficient of M‐CSF‐derived macrophages. They are severely monocytopenic, and their remaining M‐CSF‐independent macrophages were shown to differ in differentiation and distinct functions when compared with phenotypicaly normal mice of the same background. It is not known if osteopetrosis mice (op/opmice) are able to mount a specific immune response against intracellular pathogens, as this would require complex effector functions by macrophages. We therefore investigated the ability of op/opmice and their M‐CSF‐independent macrophages to combat infection with Leishmania major. op/opmice retained the ability to resist an infection with L. majorby mounting a T helper cell type 1 cell response, eliminating parasites and resolving the lesions. Macrophages from op/opmice were able to sufficiently perform effector functions in vitro, such as phagocytosis, production of leishmanicidal nitric oxide (NO), killing of parasites, and release of interleukin (IL)‐12. There were quantitative differences, as M‐CSF‐derived macrophages from hematopoietic organs of control mice showed significantly higher rates of phagocytosis and higher NO release after stimulation with lipopolysaccharides than corresponding macrophages from op/opmice. In contrast, when peritoneally elicited macrophages were used, those from op/opmice revealed a stronger response than those from control mice with regard to release of NO or IL‐12. These differences suggest that M‐CSF‐independent maturation of op/opmonocytes subsequent to their release from hematopoietic tissue exerts influence on their effector functions. However, M‐CSF or M‐CSF‐derived macrophages are not necessary for an effective immune response against L. major. |
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