Neutrophil gelatinase associated lipocalin a proinflammatory polypeptide necessary for host cell survival in bacterial infection

Abstract

During sepsis along with the manifestation of symptoms, there are many biochemical and physiological changes in the host. To mark a few are, Presence of bacteria, changes in overall proteomics of blood, which is termed acute phase response and organ failure leading to death in extreme cases. In search of biomarkers during early bacterial infection, we could identify a prominent biomarker Neutrophil gelatinase-associated lipocalin (NGAL) and its involvement in bacterial infection. NGAL is a 25 kDa protein secreted by neutrophils, whose importance is well studied in kidney injury and cancer, whereas its role during bacterial infection is less sorted. To evaluate its role, human whole blood cells (HWBC) induced with bacterial E. coli LPS were analyzed for changes in NGAL expression. NGAL transcripts were observed to be upregulated very early, <4 h of induction and continued to be detected until 18 h, after which its levels rapidly decreased by 24 h. Treatment of HWBC with steroid hormones such as estrogen (β Estradiol), testosterone, progesterone, and adrenaline confirmed the mode of action of NGAL as pro-inflammatory. Further, immunoblotting of lysates from HWBC treated with retinol and LPS revealed that upregulation of NGAL in the presence of retinol was reversed on induction with LPS. Organic extracts from the root of the plant Desmotrichum fimbriatum (DF) were explored for their effect on bacterial infection by E. coli (ATCC25922) and effect on NGAL. HWBC pre-treated with DF and induced with E. coli inhibited bacterial growth and multiplication combined with elevated NGAL and protected cells from undergoing apoptosis. This demonstrates the role of NGAL, suggesting its necessity in the host to mount antibacterial action and aid host survival. Accordingly, NGAL can be categorized as an acute phase pro-inflammatory polypeptide necessary for establishing an early immune response toward invading bacterial infection by exerting antibacterial activity necessary for cell survival.