Biology Reference
In-Depth Information
is not known. There has been a suggestion that cocaine alters the function of
NK cells, T cells, neutrophils, and macrophages and alters the ability of these
cells to secrete cytokines. In addition, cocaine enhances the infectivity and/or
replication of HIV when tested using human cells in vitro ( Baldwin et al.,
1998).
A study examined the role of IFN-g production and HIV progression. IFN-g
production was measured in 223 HIV
and 99 healthy HIV
ÿ
individuals after
4±5 h of phytohemogglotinin stimulation. IFN-g production was followed for a
median of 2.9 years. The production of IFN-g was highly increased in the blood
of HIV-infected individuals without AIDS, but decreased in the blood of AIDS
patients compared with controls. In the HIV-infected patients, the production
of IFN-g correlated with the number of CD8
T cells and CD16
, CD56
NK
cells. Low levels of IFN-g production were associated with an increased risk of
experiencing a CD4 count below 100 cells/mm
3
and death. This ®nding sug-
gests that changes in IFN-g seem to be related to the risk of disease progression
and HIV infection (Ullum et al., 1997).
A study examined how non-MHC-restricted cytotoxicity changed with re-
spect to progression and duration of HIV infection. The major ®nding was
that a low percentage of number of NK cells was found in the group that has
a rapid progression to AIDS compared with those progressing more slowly
to AIDS. Furthermore, a signi®cant correlation was found between the num-
ber of months from zero conversion to diagnosis of AIDS and percentages of
CD16
CD56
, and CD16
CD56
cells. This ®nding reveals that a low con-
centration of NK cells in the blood was associated with a more rapid disease
progression, indicating that the defective non-MHC-restricted cytotoxicity may
be associated with HIV disease progression (Bruunsgaard et al., 1997).
To perform NK functions, the NK cells must adhere, migrate, and perform
their function. Normally, NK cells localize in lungs, liver, and spleen after sys-
temic administration in rats. The NK cells are not found in peripheral lymph
nodes or splenic white pulp. However, NK cells can be modulated in both
lymph node and non-lymph node organs after administration of biologic re-
sponse modi®ers. Thus, chemoattractants are implicated. Chemotactic cyto-
kines (chemokines) are proin¯ammatory mediators necessary for the recruit-
ment of various cell types to the in¯ammatory sites (Rollins, 1997; Murphy,
1994). Chemokines are divided into four subfamilies: CXC (alpha), CC (beta),
C (gamma), and CX3C, depending on the presence and arrangement of the ®rst
cysteine residues in the amino terminal region. Chemotaxis of NK cells has
been shown to be mediated by many members such as MIP-a, RANTES,
MCP-1, MCP-3, IP-10, SDF-1a, etc. (Allavena et al., 1994; Godiska et al.,
1997; Hedrick et al., 1997). There is evidence that chemokine receptors are
coupled to heterotrimeric G proteins in NK cell membranes. In addition, a
cross-talk among the various subunits and subtypes of these G proteins is
obligatory for initiating the mobility of NK cells. In addition to G protein-
coupled receptors, receptor tyrosine kinases transmit intracellular signals re-
sulting in the activation of common secondary messengers. Chemokines not
