Neutrophil gelatinase-associated lipocalin (NGAL): Endogenous activators of the immune system (89.15)

Abstract Neutrophil gelatinase-associated lipocalin (NGAL), also known as Lipocalin 2 (Lcn2), is a member of the extremely diverse family of molecules called lipocalins. Recent studies have shown that NGAL is secreted by multiple cell types including neutrophils, and has a wide variety of functions from anti-apoptotic signaling to kidney development. We have been investigating the properties of four different forms of NGAL to determine whether they exhibit the characteristics of an alarmin. Alarmins are endogenous antimicrobial peptides or proteins which are released in response to tissue injury or infection and have the additional capacity to recruit and activate antigen presenting cells (APCs) and enhance antigen specific immune responses in vivo. Our results show that different variants of NGAL are potent stimulants of antigen presenting cells. Treatment of monocyte-derived iDCs with NGAL induced their maturation as evidenced by upregulated surface markers (CD80, CD83, CD86, and MHC class II), enhanced production of cytokines (IL-6, CXCL8, IL-12p70, and TNF alpha), and acquisition of the capacity to stimulate allogeneic T cell proliferation. Thus, NGAL can rapidly mobilize and activate pro-inflammatory innate immune responses and by generating mature DCs can also induce adaptive immune responses. If these NGAL molecules are shown to induce a significant immune response, they may prove to be useful as non-toxic vaccine adjuvants for treatment of various types of tumors.