Neuronal nicotinic alpha7 receptors modulate early neutrophil infiltration to sites of skin inflammation.
BACKGROUND
A major site of initiation of inflammatory responses upon physical perturbation(s) and infection by invading organisms is the skin. Control of responses in this organ is, in part, modulated by the neuronal nicotinic acetylcholine receptor (nAChR) alpha7.


METHODS
To further investigate the role of alpha7 in skin inflammatory responses, a local inflammatory response was induced by topical application of croton oil to the ear skin of wild-type (alpha7WT) and alpha7 knock-out (alpha7KO) mice. Cells infiltrating the inflamed tissue were characterized by flow cytometry and RNA analysis.


RESULTS
Six hours following croton oil application, analysis of infiltrating cells showed that the alpha7KO mice exhibited a significantly enhanced number of cells, and specifically, of Ly6G positive neutrophils. Macrophage and lymphocyte infiltration was equivalent in the alpha7KO and alpha7WT mice. RNA analysis showed that IL-1beta and IL-6 were increased significantly in the infiltrating cells of the alpha7KO mouse, although TNF failed to reach significance. In contrast, resident cells of the skin exhibited no differences in these cytokines between genotypes. Both resident and infiltrating cell populations from alpha7KO mice did show elevated message levels for the adhesion protein ICAM1. Measurement of chemokines revealed enhanced expression of the skin-related CCL27 by resident cells in alpha7KO mice. Further, we demonstrate that the population of Ly6G+ neutrophils at the croton oil-inflamed skin site expresses low levels of CCR10, a receptor for CCL27 normally associated with lymphocytes.


CONCLUSIONS
nAChRalpha7 in the skin can impact on early local inflammatory responses mediated through a novel population of neutrophils that are Ly6G+CCR10lo.
Gahring
Lorise C
LC
Geriatric Research, Education and Clinical Center, Salt Lake City VA Medical Center, USA. Lorise.Gahring@hsc.utah.edu
Osborne
Amber V
AV
Reed
Michelle
M
Rogers
Scott W
SW
D000818:Animals; D018925:Chemokines / Q000276:immunology; D003436:Croton Oil / Q000494:pharmacology; D003872:Dermatitis / Q000276:immunology / Q000473:pathology; D003879:Dermatologic Agents / Q000494:pharmacology; D007249:Inflammation / Q000276:immunology*; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046228:Microarray Analysis; D009474:Neurons / Q000166:cytology / Q000276:immunology*; D020556:Neutrophil Infiltration / Q000502:physiology*; D054447:Receptors, CCR10 / Q000276:immunology; D011978:Receptors, Nicotinic / Q000235:genetics / Q000502:physiology*; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D064569:alpha7 Nicotinic Acetylcholine Receptor
C515707:Ccr10 protein, mouse; D018925:Chemokines; C579166:Chrna7 protein, mouse; D003879:Dermatologic Agents; D053583:Interleukin-1beta; D015850:Interleukin-6; D054447:Receptors, CCR10; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D003436:Croton Oil