Model of cell activation and desensitization by surface immunoglobin: the case of histamine release from human basophils

Journal Article · Fri Oct 31 23:00:00 EST 1980 · Cell; (United States)

DOI:https://doi.org/10.1016/0092-8674(80)90154-3· OSTI ID:6319281

Dembo, M; Goldstein, B

We present a model for the control of immunoglobulin E (IgE)-mediated histamine release from human basophils. We suggest that there is a calcium gating factor which interacts with crosslinked IgE to form a short-lived open calcium channel. After formation of the channel the activated gating factor rapidly decays to an inactive form. It is the loss of the active gating factor which causes the basophil to desensitize nonspecifically. We propose that the crosslinked IgE molecules are deactivated by a mechanism, such as endocytosis or shedding, which is independent of the mechanism which inactivates the calcium gating factor. This loss of functional IgE leads to specific desensitization. The mathematical formulation of the model explains the relationship of specific and nonspecific desensitization to the amount of specific IgE on the basophil surface; explains why there are two types of antigen excess inhibition; explains the relationship between antigen excess inhibition and desensitization; explains why, for a fixed antigen concentration, increasing the concentration of cell surface IgE increases histamine release until an optimal concentration is reached, then decreases histamine release; predicts the effects that changing the external calcium will have on the dose response curve; and predicts that increasing the amount of specific IgE on the cell surface will cause the dose response curve to undergo a transition from a curve with a single maximum to a curve with two maxima.

• Research Organization: Los Alamos Scientific Lab., NM
• OSTI ID: 6319281
• Journal Information: Cell; (United States), Journal Name: Cell; (United States) Vol. 22; ISSN CELLB
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
550300 -- Cytology
59 BASIC BIOLOGICAL SCIENCES
ALKALINE EARTH METALS
AMINES
ANIMALS
ANTIGENS
AZOLES
BASOPHILS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL MATERIALS
BIOLOGICAL MODELS
BIOLOGICAL PATHWAYS
BIOLOGY
BLOOD
BLOOD CELLS
BODY FLUIDS
CALCIUM
CYTOLOGY
DOSE-RESPONSE RELATIONSHIPS
DYNAMIC FUNCTION STUDIES
ELEMENTS
GLOBULINS
HETEROCYCLIC COMPOUNDS
HISTAMINE
IMIDAZOLES
IMMUNE REACTIONS
IMMUNOGLOBULINS
KINETICS
LEUKOCYTES
MAMMALS
MAN
MATERIALS
MATHEMATICS
METALS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PRIMATES
PROTEINS
REACTION KINETICS
VERTEBRATES