erythrocytes into circulation every minute. The
EPO stimulates the bone marrow to release higher
numbers of erythrocytes into the blood circula-
tion, which boosts the amount of HEMOGLOBINand
increases the blood’s capacity to carry oxygen.
EPO production falters in serious kidney dis-
ease, resulting in ANEMIA. Medications that dimin-
ish kidney function may have similar effects. The
liver and perhaps other sites in the body also pro-
duce small amounts of EPO, though not enough
to meet the body’s needs when the kidneys fail.
Some people experience fluctuations in EPO pro-
duction, both increases and decreases, after KIDNEY
TRANSPLANTATION.
During the 1980s researchers identified and
sequenced the GENEresponsible for EPO, allowing
the synthesis of recombinant erythropoietin in the
laboratory. Administered by injection, this form of
EPO, epoetin alpha (Procrit, Epogen), can supple-
ment or replace endogenous EPO to stimulate the
bone marrow when kidney production falls off or
other circumstances cause rapid ERYTHROCYTE
depletion and corresponding anemia. Potential
side effects of EPO supplementation include
increased BLOOD PRESSURE(HYPERTENSION) especially
when the cause of anemia is RENAL FAILURE, and
thrombosis (the formation of blood clots within
the blood vessels) resulting from the increased
percentage of erythrocytes in the blood.
See also BLOOD DOPING; CYTOKINES; HEMATOPOIESIS;
MULTIPLE MYELOMA.
granulocyte A type of LEUKOCYTE (white BLOOD
cell) so named because its cytoplasm contains
granules. The granules, called lysosomes in neu-
trophils, contain enzymes that digest proteins and
carbohydrates, the basic components of cellular
structures. Granulocytes are primarily phagocytic;
their responsibility is to consume pathogens that
lymphocytes and other leukocytes neutralize as
part of the body’s IMMUNE RESPONSE. Pathologists
refer to granulocytes as polymorphonuclear
(PMN) because the nucleus of a granulocyte con-
tains multiple lobes. Granulocytes have a short life
span in the circulation, typically six to eight hours.
After this time some of them migrate into the tis-
sues and continue to function as phagocytes. The
liver filters from circulation those that do not
migrate and its phagocytic cells, the Kupffer cells,
consume them. There are three types of granulo-
cytes, named for the kinds of tissue dyes they
accept to emphasize their structures for micro-
scopic examination: basophils, eosinophils, and
neutrophils.
BasophilsA basophil accepts a base dye such as
methylene blue, accounting for its name, which
means “base-loving.” Basophils respond to the var-
ious chemicals injured cells and pathogens release,
among them HISTAMINE, serotonin, CYTOKINES,
LEUKOTRIENES, and PROSTAGLANDINS. Basophils them-
selves also release these chemicals, which serves to
further incite an inflammatory response as well as
summon more leukocytes into action. Basophils
filled with HISTAMINEgranules are primarily respon-
sible for HYPERSENSITIVITY REACTION and ALLERGY
responses. They are abundant in the bronchial tis-
sues during ASTHMAattacks, for example, and in the
tissues surrounding an insect bite or sting.
Eosinophils The eosinophil (“eosin-loving”)
accepts a tissue dye called eosin for examination
under the light microscope. Eosinophils, contain-
ing enzymes to digest bacteria and other
pathogens, also have roles in histamine release
(such as in hypersensitivity reactions and asthma)
and inflammatory response. Parasitic infections,
atopic DERMATITIS, non-Hodgkin’s LYMPHOMA, and
OVARIAN CANCERare among the conditions that can
cause elevated eosinophil levels. Medication reac-
tions, notably with beta blockers and CORTICO-
STEROID MEDICATIONS, are among the causes of
lowered eosinophil levels. An eosinophil normally
circulates about eight hours in the blood and then
migrates into the tissues.
NeutrophilsThe neutrophil (“neutral-loving”)
stains neutrally for microscopic examination. It is
the most abundant type of leukocyte in the blood,
making up about 70 percent of the white blood cells
in circulation. Neutrophils are the IMMUNE SYSTEM’s
infantry, maintaining a strong defensive presence
in the blood and swarming to attack invading
pathogens. Neutrophils that die in the line of duty
release toxic chemicals to continue their protective
actions. Neutrophils are integral to the body’s
inflammatory response and are often to blame for
autoimmune attacks such as those that occur with
RHEUMATOID ARTHRITISand INFLAMMATORY BOWEL DIS-
EASE(IBD). Numerous health conditions can lower
the number of neutrophils in the blood circulation138 The Blood and Lymph