When a hungry mosquito zooms in for a landing on a runway ofexposed skin, it sucks up a meal of blood, then takes off. Thequestion is: Why doesn't that bloodthirsty, itch-making parasite hangin and keep on sucking?
The answer is an immune-system bouncer called the mast cell. Whenthe mosquito sticks its hollow-needle nose into its victim's skin, mastcells swarm to the site and release chemical factors that the parasitecan't stand.
This cellular insect repellent, the mast cell, has a lot of other bodilyfunctions, some useful, others harmful, most of them unclear.
Mast cells are so-called after the German word masten, meaning"food-fattened." Bacteriologist Paul Ehrlich, one of immunology'sfounding fathers, discovered these cells in 1877. He named them"food fatteners" because of the plump granules that stuff the jumbocells' cytoplasm.
Besides mosquito-chasing molecules, mast-cell granules contain ahost of immune factors, the most nefarious being histamine. Fromsneezing to wheezing, from common cold to hay fever to asthma,histamine is largely responsible for the misery of allergic disorders.
But mast cells have an even more sinister ill to answer for _anaphylaxis. This is the often fatal reaction that follows a rush ofover-secreted mast cells triggered by a bee sting, monosodiumglutamate seasoning or other excessive response to an immune-system insult.
And then there's mast cell leukemia, in which these outsize cellsreally go out of control.
Besides uncertainty as to what mast cells are good for, what theirnatural function is, their very origin in the body remains a partialmystery. It's known that they arise from the hematopoietic (blood-forming) stem cells of the bone marrow, and migrate to take upstations throughout the body's mucosal or connective tissue.
But just which stem cells differentiate to create mast cell precursors,and when in the course of mammalian gestation this takes place, hasbeen keeping research immunologists busy for decades.
One such scientist is Hans-Reimer Rodewald, a member of the BaselInstitute for Immunology in Switzerland. He has just found such acellular ancestor, as announced in today's Science. The paper, ofwhich he is first author, bears the title: "Identification of a committedprecursor for the mast cell lineage."
Rodewald told BioWorld Today that "this is actually the earliest celltype of this lineage that has been found so far. It's very close to astem cell, but already a mast cell precursor."
Seek Not And Thou Shalt Find
The Basel-based researcher had been working on mast cellprogenesis in mouse fetal blood for the last couple of years, and said,"Actually, I was not searching for this type of cell.
"As a matter of fact," he explained, "if you wanted to search for it,you couldn't find it, because you wouldn't know where to start. I wasjust curious to see whether or not you could purify progenitors fromfetal blood, and whether they were stem cells or committedprecursors."
A senior co-author of the Science article, experimental pathologistAnn Dvorak, observed: "The beauty of this system is that Rodewaldwas accessing fetal blood, so this is the new twist that I hadn't gotbefore." Dvorak, who is in the pathology department at Boston'sBeth Israel, a Harvard teaching hospital, is preeminent in mast cellresearch.
She scoped Rodewald's cellular specimens with ultra-structuraltransmission electron microscopy. Dvorak told BioWorld Today, that"we identified his in vivo cells as showing the granules andorganelles of an authentic mast cell lineage." She added,"Rodewald's accessing embryonic tissues is a real tour de force _just getting enough of them for these studies."
Rodewald concurred. "Mouse fetal blood," he said, "is a scarcesource, very rare. Only 20 microliters per fetus. I had to use 50 to 100to get maybe 5,000 of these cells."
As for extrapolating from mouse to human, he observed: "Humanfetal blood is not the most accessible material, for obvious reasons.Once we have found a similar procedure to isolate these mast cellprecursors from adult mouse blood, then maybe one can also go tohuman blood." But whether the two species are equivalent, he added,"we cannot say. I think the chance is very high, but it's purespeculation."
He does note one mouse/human parallel. "There's one human mastcell tumor line that is phenotypically similar in some respects to whatwe describe [for mice]."
Mast-Minus Mice Confirm Fetal Cell Lineage
Other mice that served to confirm the mast cell lineage are rodentsthat lack mast cells altogether. These animals are not geneticallyengineered knockouts but wild-type mutants _ what Dvorak called"experiments of nature." Experimental pathologist Stephen Galli,director of pathology research at Beth Israel, and a co-author of theScience paper, collaborated with Rodewald in testing these mice.
When Rodewald injected his mast cell precursors into the bellies ofsuch mice, Science reported, "this population reconstituted theperitoneal mast cell compartment of genetically mast cell-deficientmice to wild-type levels."
Allergic stimuli, Rodewald pointed out, reach mast cells viaimmunoglobulin E. (IgE) "They are the key cell type," he said,"which releases granules through the IgE receptor." In his gestationalprecursor cells, he added, "we found that some proteases, which aretypical of mast cells, are already expressed at this early stage, but thecells are not triggerable through the normal receptor, because theydon't yet have that receptor."
Dvorak observed that "There are lots of places where people haveseen mast cells. I've certainly spent my life looking at them in humandisease. In recent years," she continued, "they've become much moreexciting because it's been determined that, in addition to histamines,they make cytokines _ which are a really hot topic."
Rodewald's discovery, Dvorak observed, "allows the world now toknow what the very least-mature progenitor in this mast cell lineagelooks like, and what its cell markers are. There's some functionaldata here too. So we're getting closer and closer to the beginning."She concluded, "The more you know about a lineage, the more youcan think about intervening in the responses that are harmful topatients." n
-- David N. Leff Science Editor
(c) 1997 American Health Consultants. All rights reserved.