Pathway to carrageenan-induced inflammation in the hind limb of the rat.
A sequential 43-step pathway scheme for the inflammatory response of the rat to interdermal injection of carrageenan (C) was devised. It consisted of a nonphagocytic inflammatory response (NPIR) followed by a phagocytic inflammatory response (PIR) in the dermis and an epidermal NPIR. The dermal NPIR comprised edema, hyperemia, and hyperalgesia followed by hypoalgesia. Antiserotonin agents inhibited the hypoalgesia and part of the edema. These findings and histological observations suggested that dermal mast cells were injured by C. The hyperalgesia and part of the edema were sensitive to arachidonate cyclooxygenase inhibitors (AACOIs). It is speculated that injured mast cells metabolize arachidonic acid and reactive intermediates, not prostaglandins, mediate the NPIR hyperalgesia and part of the edema. The dermal PIR consisted of mobilization of neutrophils, edema, hyperalgesia, mobilization of monocytes, and proliferation of fibroblasts and vascular tissue. Selective drug actions revealed that the edema, hyperalgesia, and monocyte mobilization of the PIR depended on the mobilization of neutrophils. After the mobilization of neutrophils, AACOIs reduced edema formation and hyperalgesia. Arachidonic acid metabolism by neutrophils is speculated to produce the mediators of phagocytic inflammatory (PI) edema and hyperalgesia. Monocyte function was associated with cessation of PI edema formation and phagocytosis of neutrophils and cellular debris. Interleukin 1 is speculated to mediate the adherence of neutrophils to injured dermal endothelium. The epidermal NPIR consisted of edema, hyperplasia, and hyperkeratosis. These parameters were not studied mechanistically. There was no evidence for histamine, bradykinin, platelets, clotting factors, or complement mediating any events in the pathway.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002351:Carrageenan / Q000633:toxicity*; D002448:Cell Adhesion; D004195:Disease Models, Animal / Q000473:pathology*; D004487:Edema / Q000139:chemically induced / Q000503:physiopathology; D004727:Endothelium / Q000473:pathology; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D008954:Models, Biological; D009504:Neutrophils / Q000502:physiology; D010587:Phagocytosis; D051381:Rats; D012701:Serotonin / Q000502:physiology; D012867:Skin / Q000473:pathology; D012871:Skin Diseases / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*
D001095:Arachidonic Acids; D016718:Arachidonic Acid; D012701:Serotonin; D002351:Carrageenan