Question

If you wanted to inhibit neutrophile accumulation at the site of an infection, What mechanism(s) that promote neutrophile accumulation would you target and why?

Answer 1

• Neutrophills are the most abundant leukocytes in the blood and they are the first line of defence when an antigen enters the host body.
• Neutrophills destroy the infectious organisms by phagocytosis,degranulation,reactive oxygen species and neutrophill traps.
• Neutrophills release cytokines, proteases and other compounds at the site of infection and also hepls to activate B and T cells.
• Neutrophills express wide variety of receptors that help in neutrophill migration ,G -protein coupled receptors ,Fc receptors,cytokine receptors,pro inflamatory mediators, chemotoxins etc. By blocking the down stream signalling path ways of these receptors can affect the neutrophill activity .
• Bocking the Neutral proteases like neutrophill elastase and cathepsin G which are required for digestion by neutrophills can inhibit neutrophill accumulation at the site of injury.
• Example: Adenosine triphosphate released from necrotic cells activated the Nlrp3 inflammasome to generate an inflammatory microenvironment that alerted circulating neutrophils to adhere within liver sinusoids.In this case blocking the ATP from nectrotic cells can prevent neutrophill accumulation.
• Blocking or inhibiting the P38 mitogen activated protein kinases MAPKS signalling pathways have antiinflamatory effects .