Association of elevated lymph node cell release of histamine and tumor necrosis factor with genetic predisposition to limb edema formation in dogs infected with Brugia pahangi.

Abstract

Brugia pahangi infection in the canine rear limb results in marked lymphatic duct and popliteal lymph node pathologic changes. Limb edema is variably associated with infection and does not correlate well with duct or node lesions. To understand the mechanisms of limb edema, lymph node cells were collected by sequential biopsy following infection and examined for production of inflammatory mediators. Lymph node cells from a litter of dogs selectively bred with a high incidence of edema formation (82%) demonstrated spontaneously released histamine and prostaglandin E2 levels higher than those of closely related nonedema-forming dogs (0-20%) and/or control dogs. These edema-forming dogs also showed elevated release of tumor necrosis factor-␣ when cells were cultured with Brugia antigen. Toluidine blue staining of infected lymph node sections revealed that the edema-forming dogs had higher numbers of mast cells than infected lymph nodes of nonedema-forming dogs.

The mast cell in wound healing

“…Recognition of their ability to respond to a composite range of stimuli, and the identification of an increasing number of biochemical mediators contained in and released by mast cells (Table 1), 7–35 has led to an extension of the functional role of these cells in an increasingly wide range of diseases, from inflammatory to parasitic disease, from fibrotic involutions to tumours 36–50 …”

“…[4][5][6] Recognition of their ability to respond to a composite range of stimuli, and the identification of an increasing number of biochemical mediators contained in and released by mast cells (Table 1), has led to an extension of the functional role of these cells in an increasingly wide range of diseases, from inflammatory to parasitic disease, from fibrotic involutions to tumours. [36][37][38][39][40][41][42][43][44][45][46][47][48][49][50] In the skin, in particular, an important role was classically reserved for the mast cell, but limited to allergic and parasitic diseases. [51][52][53][54] Later, as a result of continual research into its functional characteristics, this cell acquired increasing importance in all processes requiring delicate biological coordination between the cells of the skin for their correct performance.…”

Immunopathogenesis of lymphatic filarial disease

“…For example, infection of cats with Brugia results in obliteration of afferent lymphatics and fibrous tissue formation in lymph nodes as well as collateral lymphatic vessel formation (65). Similarly, infections of dogs with Brugia results in limb edema, which is associated with increased spontaneous levels of histamine and prostaglandin E2 and increased filarial antigen driven TNF-α (66). Pro-inflammatory cytokines of innate origin also appear to play an important role in brugian infection since infection of nude mice results in elevated levels of IL-1, IL-6, TNF-α and GM-CSF in lymph fluid (67).…”