Synergistic activation of leukocytes by bacterial chemoattractants: potential drug targets

Accumulating evidence demonstrates that bacterial chemoattractants not only attract leukocytes (chemotaxis) but also contribute directly to inflammation by activation of leukocytes to produce a variety of pro-inflammatory cytokines. Recent studies have shown that mixtures of the bacterial chemoattractant fMLP (N-formyl-Met-Leu-Phe) and other bacterial products/components such as LPS (lipopolysaccharide) behave synergistically in activating leukocytes. These results suggest that inflammatory responses are induced by multiple inducers that operate synergistically through multiple signaling pathways. This synergy is likely to play a significant role in the induction of host defense to bacterial infections and in the pathogenesis of inflammatory disorders. These results also demonstrate that the control of inflammation is likely best understood at the level of synergistic regulation of intracellular signaling. The use of pharmacological inhibitors to modulate synergistic molecules is therefore an attractive possibility for the treatment of inflammatory disease. In this review, we will provide a brief summary of recent studies on the regulation of leukocyte functioning by bacterial chemoattractants.