living bacteria: these are the three apidaecins la,
Ib and II, which differ from each other in only 2
of their 18 amino acids, and the larger abaecin
with 34 amino acids [29]. "Sapecin" from tissue
cultures of the fly S. peregrina, and "phormicin"
from the haemolymph of P. terranovae are specific
for Gram-positive bacteria. In view of the similarities in their 40-amino-acid sequence and the
positions of three disulphide bridges to the antibacterial "defensins" from neutrophil blood cells
and mammalian macrophages, these proteins are
better termed insect defensins [41, 86, 97, 112].
The same family includes the antibacterial protein royalisin (51 amino acids) from the royal jelly
of the honeybee [52].
Very little is known about the antibacterial proteins of other invertebrates. Of the annelids,
most attention has been paid to the oligochaete
Eisenia foetida, whose coelom fluid has an unusually high protein concentration of 4-6 mg/l. Several protein components are normally present
which not only lyse (haemolysins) or agglutinate
(haemagglutinins) the erythrocytes of various vertebrates but also have bacteriostatic effects. The
haemolysins, which are also bactericidal, have
molecular masses of 40-45 kDa and show pronounced genetic polymorphism; they are produced in the chloragocytes. The haemagglutinins
(lectins) have sizes between 11.5 and 40 kDa,
with the larger components also having haemolytic properties. In the case of the earthworm
Lumbricus terrestris, the coelom fluid presents a
spectrum of multiple haemolysins and agglutinins
after immunization with mammalian erythrocytes
or inoculation with bacteria [88, 150, 178]. Lysozymes have also been detected in the coelom fluid
of various annelids [17, 71, 88]. The haemocytes
of the Japanese horseshoe crab Tachyp/eus tridentatus produce a basic peptide of 17 amino acids
known as tachyplesin; this has an antibacterial
action against both Gram-positive and Gramnegative bacteria. Similarly to the antilipopolysaccharide (LPS) factor from T. tridentatus and the North American xiphosuran Limulus
polyphemus (102 amino acids; see p. 206), tachyplesin also inhibits haemolymph clotting caused
by bacterial LPS [169].
6.9 Immune-Reactive Proteins
of the Cell Surface
Animal cells are able to recognize and bind to
other cells of the same type or to certain other
6.9.1 Cell-Adhesion Molecules of Vertebrates
237
cells of their own bodies, as has been clearly
shown in cell aggregation experiments. Adhesive
interactions between the same or different cells
playa vital role in the processes of morphogenesis
and tissue development [5, 123]. Cell-adhesion
molecules are involved in the interaction between
egg and sperm in fertilization. The proteins on the
surface of parasitic protozoans have been intensively investigated for medical reasons. In intracellular species of parasites they are responsible
for attachment to the host cell. For protozoans
parasitizing vertebrates, it is the surface proteins
which are the target for immune defence, and
several protozoan species have evolved mechanisms to avoid the defence reactions of their host.
6.9.1 Cell-Adhesion Molecules of Vertebrates
The proteins involved in the linking of vertebrate
cells to each other and to the extracellular matrix
are divided into three groups according to function: cell-adhesion molecules (CAMs), celljunction proteins (CJMs) and matrix- or substrateadhesion molecules (SAMs). The SAMs include
not only the receptor molecules of the cell surface
but also the components of the intracellular matrix with which they interact, e.g. collagens, laminin, fibronectin and glycosamineglycans; these
are discussed elsewhere in this book. The amino
acid sequences derived from cDNA clones are
known for many of these adhesion molecules.
They often contain sequence motifs that are repeated several times and are known from other proteins, e.g. the Ig homology units of about 100
amino acids, the equally long type-III fibrinogen
domains, EGF-like domains of about 40 amino
acids, or calcium-binding regions with numerous
Asp, Asn, Thr or Ser residues. The tripeptide
sequence Arg-Gly-Asp (RGD sequence) is widely
found in proteins of the extracellular matrix and in
the corresponding receptors [5]. Electron micrographs reveal very complex three-dimensional
structures for many of the adhesion molecules,
with globular regions, stiff rods and flexible
threads; it is assumed that the different structural
elements have different functions [5].
The functional category of the CAMs includes
proteins from two different super-families: the Ig
super-family and the cadherin family. The bestknown CAM of the I G super-family is N -CAM
(N for neuronal), which already appears on neurons early in embryo development and is later to
be found on other cell types. N-CAM is homophilic, i.e. the N-CAM of one cell binds to
Ib and II, which differ from each other in only 2
of their 18 amino acids, and the larger abaecin
with 34 amino acids [29]. "Sapecin" from tissue
cultures of the fly S. peregrina, and "phormicin"
from the haemolymph of P. terranovae are specific
for Gram-positive bacteria. In view of the similarities in their 40-amino-acid sequence and the
positions of three disulphide bridges to the antibacterial "defensins" from neutrophil blood cells
and mammalian macrophages, these proteins are
better termed insect defensins [41, 86, 97, 112].
The same family includes the antibacterial protein royalisin (51 amino acids) from the royal jelly
of the honeybee [52].
Very little is known about the antibacterial proteins of other invertebrates. Of the annelids,
most attention has been paid to the oligochaete
Eisenia foetida, whose coelom fluid has an unusually high protein concentration of 4-6 mg/l. Several protein components are normally present
which not only lyse (haemolysins) or agglutinate
(haemagglutinins) the erythrocytes of various vertebrates but also have bacteriostatic effects. The
haemolysins, which are also bactericidal, have
molecular masses of 40-45 kDa and show pronounced genetic polymorphism; they are produced in the chloragocytes. The haemagglutinins
(lectins) have sizes between 11.5 and 40 kDa,
with the larger components also having haemolytic properties. In the case of the earthworm
Lumbricus terrestris, the coelom fluid presents a
spectrum of multiple haemolysins and agglutinins
after immunization with mammalian erythrocytes
or inoculation with bacteria [88, 150, 178]. Lysozymes have also been detected in the coelom fluid
of various annelids [17, 71, 88]. The haemocytes
of the Japanese horseshoe crab Tachyp/eus tridentatus produce a basic peptide of 17 amino acids
known as tachyplesin; this has an antibacterial
action against both Gram-positive and Gramnegative bacteria. Similarly to the antilipopolysaccharide (LPS) factor from T. tridentatus and the North American xiphosuran Limulus
polyphemus (102 amino acids; see p. 206), tachyplesin also inhibits haemolymph clotting caused
by bacterial LPS [169].
6.9 Immune-Reactive Proteins
of the Cell Surface
Animal cells are able to recognize and bind to
other cells of the same type or to certain other
6.9.1 Cell-Adhesion Molecules of Vertebrates
237
cells of their own bodies, as has been clearly
shown in cell aggregation experiments. Adhesive
interactions between the same or different cells
playa vital role in the processes of morphogenesis
and tissue development [5, 123]. Cell-adhesion
molecules are involved in the interaction between
egg and sperm in fertilization. The proteins on the
surface of parasitic protozoans have been intensively investigated for medical reasons. In intracellular species of parasites they are responsible
for attachment to the host cell. For protozoans
parasitizing vertebrates, it is the surface proteins
which are the target for immune defence, and
several protozoan species have evolved mechanisms to avoid the defence reactions of their host.
6.9.1 Cell-Adhesion Molecules of Vertebrates
The proteins involved in the linking of vertebrate
cells to each other and to the extracellular matrix
are divided into three groups according to function: cell-adhesion molecules (CAMs), celljunction proteins (CJMs) and matrix- or substrateadhesion molecules (SAMs). The SAMs include
not only the receptor molecules of the cell surface
but also the components of the intracellular matrix with which they interact, e.g. collagens, laminin, fibronectin and glycosamineglycans; these
are discussed elsewhere in this book. The amino
acid sequences derived from cDNA clones are
known for many of these adhesion molecules.
They often contain sequence motifs that are repeated several times and are known from other proteins, e.g. the Ig homology units of about 100
amino acids, the equally long type-III fibrinogen
domains, EGF-like domains of about 40 amino
acids, or calcium-binding regions with numerous
Asp, Asn, Thr or Ser residues. The tripeptide
sequence Arg-Gly-Asp (RGD sequence) is widely
found in proteins of the extracellular matrix and in
the corresponding receptors [5]. Electron micrographs reveal very complex three-dimensional
structures for many of the adhesion molecules,
with globular regions, stiff rods and flexible
threads; it is assumed that the different structural
elements have different functions [5].
The functional category of the CAMs includes
proteins from two different super-families: the Ig
super-family and the cadherin family. The bestknown CAM of the I G super-family is N -CAM
(N for neuronal), which already appears on neurons early in embryo development and is later to
be found on other cell types. N-CAM is homophilic, i.e. the N-CAM of one cell binds to