LAMP‐1 and LAMP‐2, but not LAMP‐3, are reliable markers for activation‐induced secretion of human mast cells

Abstract

BackgroundMast cells are resident tissue cells that induce anaphylactic reactions by rapidly releasing mediators after antigen‐mediated cross‐linking of immunoglobulin E receptors. In the similarly active peripheral blood basophilic leukocyte, lysosome‐associated membrane protein 3 (LAMP‐3; CD63) has been described as an activation marker, but LAMPs have not been investigated in normal tissue mast cells.MethodsIntra‐ and extracellular expressions of LAMP‐1 (CD107a), LAMP‐2 (CD107b), and LAMP‐3 (CD63) were analysed by flow cytometry, immunocytochemistry, and functional assays in unstimulated and stimulated leukemic human mast cell line 1 (HMC‐1) and skin mast cells.ResultsOn flow cytometry, all mast cells expressed LAMP‐3 at their cell membranes, whereas LAMP‐1 and LAMP‐2 were barely detectable (HMC‐1 cells) or expressed at low levels (<10% of skin mast cells). After fixation and permeabilisation, high intracellular levels of all three LAMPs were noted in both cell types. After stimulation, a rapid translocation of intracellular LAMPs to the cell membrane, with an associated release of histamine, leukotriene C4 and prostaglandin D2, was ascertained in skin mast cells only.ConclusionThese results show that LAMP‐1 and LAMP‐2 are activation markers for normal mast cells. The lack of LAMP translocation after activation of leukemic mast cells may be related to maturation or malignancy‐associated defects of these cells. © 2004 Wiley‐Liss, Inc.

Identification of CD13, CD107a, and CD164 as novel basophil-activation markers and dissection of two response patterns in time kinetics of IgE-dependent upregulation

“…Very recently, CD107a and CD107b were also identified as reliable activation markers for human mast cells. After stimulation with anti-IgE, a rapid translocation of cytoplasmic CD107 molecules to the cell membrane associated with a release of histamine, leukotriene C 4 , and prostaglandin D 2 , was observed [51]. In the current study, we describe a new subset of immune effector cells with an activationinduced expression of CD107a and -to a weaker extent -CD107b.…”

“…Recently, the structurally related lysosome-associated membrane proteins-1 and -2 (LAMP-1 and LAMP-2; CD107a and CD107b) have been identified as activation markers in a variety of cells [36][37][38][39][51][52][53]. Thus, both molecules were reported to be expressed on activated but not resting platelets, and CD107a was shown to be expressed exclusively on cytotoxic NK effector cells but not on other NK cell subsets [53].…”

The LAMP Story and What It Means for ANCA Positive Vasculitis in Nephrology

“…Possible additional roles of LAMP-2 as a diagnostic marker need to be investigated further -conceivably it might play a role as a tumour marker as well as in screening of newborns for presymptomatic lysosomal storage disease: In a study LAMP-2 plasma concentrations were increased in >66% of patients with lysosomal storage disorders 63 , and the increases coincided with increased LAMP-1 concentrations. Increased LAMP-1 and -2 levels have been associated with normal mast cell activation 64 , increased LAMP-2 expression in peripheral leucocytes with coronary artery disease 65 . There seems to be the possibility of a non-genetic, acquired LAMP-2 deficiency in alcoholic acute pancreatitis or severe endotoxemia 66 .…”

Genome-wide association study of serious blistering skin rash caused by drugs

“…LAMP1 encodes for a lysosome-associated transmembrane glycoprotein, which is a marker of both CD8 þ lymphocytes 35 and skin mast cell activation. 36 The glycoprotein also seems to be implicated in antigen presentation through major histocompatibility complex. 37,38 We demonstrated that the power of an association study is greatly improved by expanding the set of controls using publicly available genotypes from individuals of the same ethnicity.…”