Loxosceles Spider Venom Induces the Production of α and β Chemokines: Implications for the Pathogenesis of Dermonecrotic Arachnidism

Abstract

Bites from the brown recluse spider and other Loxosceles arachnids result in dermonecrotic skin lesions. Neutrophils (PMN) are essential to the development of Loxosceles -induced skin lesions, but paradoxically, in vitro PMN activation is inhibited by direct exposure to Loxosceles venom. Neutrophil activation occurs in response to a myriad of soluble mediators that include members of both the α and β chemokine families. Because arachnid envenomation results in the exposure of several different cell types to venom, we investigated venom-induced expression of α and β chemokines in both endothelial cells (human umbilical vein; HUVEC) and epithelial cells (A549 pneumocytes). Chemokine-specific capture enzyme immunoassays (EIA) were used to measure Loxosceles deserta venom-induced α chemokines: interleukin-8 (IL-8), growth-related oncogene-alpha (GRO-α), and β chemokines: monocyte chemoattractant protein-1 (MCP-1), and regulated on activation, normal T cell expressed and secreted (RANTES) in cell-free conditioned media from HUVEC and A549 cell monolayers. Exposure of HUVECs (8 h) to Loxosceles venom resulted in the production of IL-8 (5.2 ± 1.30 ng/ml), MCP-1 (1.44 ± 0.11 ng/ml) and GRO-α (1.97 ± 0.15 ng/ml) in a dose and time-dependent manner. Exposure of A549 cell monolayers to venom resulted in IL-8 (7.74 ± 0.30 ng/ml), and MCP-1 (2.61 ± 0.31 ng/ml), but neither GRO-α nor RANTES accumulated during an 8-hour incubation period. Chemokines accumulated in a venom dose and time-dependent manner. Neither cell type secreted RANTES in response to Loxosceles venom. These data indicate that Loxosceles spider venom is a potent inducer of α and β chemokines in both endothelial and epithelial cell types. Based on the established roles of IL-8, MCP-1, and GRO-α, in inflammation, these observations have relevance to the pathophysiology of Loxosceles -Induced dermonecrosis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44524/1/10753_2004_Article_408823.pd